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  • Title: Change of expression levels of alpha1-adrenoceptor subtypes by administration of alpha1d-adrenoceptor-subtype-selective antagonist naftopidil in benign prostate hyperplasia patients.
    Author: Kojima Y, Sasaki S, Shinoura H, Hayase M, Kubota Y, Hayashi Y, Tsujimoto G, Kohri K.
    Journal: Prostate; 2007 Sep 01; 67(12):1285-92. PubMed ID: 17626248.
    Abstract:
    BACKGROUND: We examined whether the change of alpha(1)-adrenoceptor (alpha(1)-AR) subtype expression levels in the prostate occurred by administration of the alpha(1d)-AR-subtype-selective antagonist naftopidil to benign prostate hyperplasia (BPH) patients, and discussed the possible alternation of its effectiveness by the chronic administration of alpha(1)-AR antagonists. METHODS: Fifteen patients with untreated BPH aged 58-76 (mean age, 68.2 +/- 7.4 years) underwent prostate biopsy from the transition zone before and after 50 mg naftopidil administration daily for 12 weeks. Taqman quantitative reverse transcription polymerase chain reaction was performed using these biopsy specimens to estimate the expression level of each alpha(1)-AR subtype. Comparison was made of the expression level of alpha(1)-AR subtypes before and after naftopidil administration. We also examined the correlation between the change of alpha(1)-AR subtype expression levels and the short-term efficacy of naftopidil. RESULTS: Naftopidil administration for 12 weeks down-regulated the expression of alpha(1a)-AR and alpha(1b)-AR mRNA and up-regulated the expression of alpha(1d)-AR mRNA without a change in the total alpha(1)-AR mRNA expression level. There was no correlation between the change of alpha(1)-AR subtype expression levels and the short-term efficacy of naftopidil for BPH patients. CONCLUSION: The change of alpha(1d)-AR expression level may be regarded as a compensatory adaptation to chronic alpha(1d)-AR antagonist naftopidil administration. This may mean that long-term use of the same alpha(1)-AR antagonist for BPH patients induces therapeutic tolerance.
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